tbuckley/cabot-search huggingface dataset:
The impact of Covid-19 in patients with chronic myeloid leukemia—a nationwide population-based study
Authors: Torsten Dahlén, Hjalmar Flygt, Anna Lübking, Ulla Olsson-Strömberg, Lovisa Wennström, Arta Dreimane, Anders Själander, Susannah Leach, Magnus Gisslén, Huiqi Li, Martin Höglund, Leif Stenke, Fredrik Nyberg
Journal: Leukemia (2023)

Since December 2019 more than 460 million confirmed cases and 6 million deaths have been attributed world-wide to coronavirus disease 2019 (Covid-19) [1].Patients with hematological cancer have been reported to suffer increased risk of severe Covid-19, with a hospitalization rate of more than 50% and a case fatality rate of approximately 30% [2].The impact of Covid-19 on patients with chronic myeloid leukemia (CML) remains uncertain [2-5].The Italian Campus CML network reported on more than 8000 CML patients and detected only 217 Covid-19 positive cases [5].However, among these cases 22% were admitted to hospital with a relatively high mortality rate of 5.5%.Similarly, a preliminary report from the CANDID study, conducted by the International CML Foundation, estimated the mortality rate among Covid-19 infected CML cases at 14% [4].Because of these somewhat diverging data, a recent review concluded that the incidence and severity of Covid-19 in CML have not yet been thoroughly investigated and called for a true population-based study [6].Our goal was to perform such a study, examining a large number of patients and comparing against carefully matched controls, utilizing high-quality full-coverage population-based registers addressing the period when Covid-19 was classified as "disease dangerous to public health" with widespread public PCR testing was available, February 1st 2020 to April 1st 2022.We utilized an existing database containing data on all Swedish individuals together with information on relevant Covid-19 outcomes (the SCIFI-PEARL project database), with information on all positive Covid-19 tests (PCR-based testing) as well as all Covid-19-related hospital and intensive care unit (ICU) admissions, deaths, and national vaccination data [7].This database specifically contains exposure and outcome information in terms of information on specialized outpatient-and all inpatient healthcare, cancer diagnoses, as well as information on all dispensed drug prescriptions [8].
DNA architectural protein CTCF facilitates subset-specific chromatin interactions to limit the formation of memory CD8+ T cells
Authors: Sara Quon, Bingfei Yu, Brendan E. Russ, Kirill Tsyganov, Hongtuyet Nguyen, Clara Toma, Maximilian Heeg, James D. Hocker, J. Justin Milner, Shane Crotty, Matthew E. Pipkin, Stephen J. Turner, Ananda W. Goldrath
Journal: Immunity (2023)
Synergistic effects of combined immunotherapy strategies in a model of multifocal hepatocellular carcinoma
Authors: Maria Carmen Ochoa, Sandra Sanchez-Gregorio, Carlos E. de Andrea, Saray Garasa, Maite Alvarez, Irene Olivera, Javier Glez-Vaz, Carlos Luri-Rey, Iñaki Etxeberria, Assunta Cirella, Arantza Azpilikueta, Pedro Berraondo, Josepmaria Argemi, Bruno Sangro, Alvaro Teijeira, Ignacio Melero
Journal: Cell Reports Medicine (2023)

Immune checkpoint-inhibitor combinations are the best therapeutic option for advanced hepatocellular carcinoma (HCC) patients, but improvements in efficacy are needed to improve response rates. We develop a multifocal HCC model to test immunotherapies by introducing c-myc using hydrodynamic gene transfer along with CRISPR-Cas9-mediated disruption of p53 in mouse hepatocytes. Additionally, induced co-expression of luciferase, EGFP, and the melanosomal antigen gp100 facilitates studies on the underlying immunological mechanisms. We show that treatment of the mice with a combination of anti-CTLA-4 + anti-PD1 mAbs results in partial clearance of the tumor with an improvement in survival. However, the addition of either recombinant IL-2 or an anti-CD137 mAb markedly improves both outcomes in these mice. Combining tumor-specific adoptive T cell therapy to the aCTLA-4/aPD1/rIL2 or aCTLA-4/aPD1/aCD137 regimens enhances efficacy in a synergistic manner. As shown by multiplex tissue immunofluorescence and intravital microscopy, combined immunotherapy treatments enhance T cell infiltration and the intratumoral performance of T lymphocytes.
Multimodal immunogenomic biomarker analysis of tumors from pediatric patients enrolled to a phase 1-2 study of single-agent atezolizumab
Authors: Arash Nabbi, Arnavaz Danesh, Osvaldo Espin-Garcia, Stephanie Pedersen, Johanna Wellum, Lingyan Helen Fu, Joseph N. Paulson, Birgit Geoerger, Lynley V. Marshall, Tanya Trippett, Gianluca Rossato, Trevor J. Pugh, Katherine E. Hutchinson
Journal: Nature Cancer (2023)

We report herein an exploratory biomarker analysis of refractory tumors collected from pediatric patients before atezolizumab therapy (iMATRIX-atezolizumab, NCT02541604 ). Elevated levels of CD8+ T cells and PD-L1 were associated with progression-free survival and a diverse baseline infiltrating T-cell receptor repertoire was prognostic. Differential gene expression analysis revealed elevated expression of CALCA (preprocalcitonin) and CCDC183 (highly expressed in testes) in patients who experienced clinical activity, suggesting that tumor neoantigens from these genes may contribute to immune response. In patients who experienced partial response or stable disease, elevated Igα2 expression correlated with T- and B-cell infiltration, suggesting that tertiary lymphoid structures existed in these patients' tumors. Consensus gene co-expression network analysis identified core cellular pathways that may play a role in antitumor immunity. Our study uncovers features associated with response to immune-checkpoint inhibition in pediatric patients with cancer and provides biological and translational insights to guide prospective biomarker profiling in future clinical trials.
Bioinspired Photonic Microchip with Molecularly Imprinted Polymer for Single Recognition of c‐Myc Protein in Predictive Medical Diagnostics
Authors: Jun Xu, Xianghui Liu, Ya Sun, Di Zhang, Han Zhou, Tongxiang Fan
Journal: Advanced Healthcare Materials (2023)

Monitoring of trace c-Myc protein as the biomarker of ubiquitous cancers is critical in achieving predictive medical diagnostics. However, qualitative and quantitative detection of c-Myc protein with superior single selectivity and sensitivity is still challenging. Herein, a bioinspired photonic sensing microchip for single recognition of c-Myc protein is outlined with two synergistic aspects involving chemical and physical design criteria. Chemical design uses specific molecularly imprinted polymer (MIP) with exquisite complementarity in its chemical functions and spatial geometries to targeted c-Myc protein, leading to excellent sensitivity and selectivity for single identification. Physical design involves optical geometrical double-reflection polarization rotation and multilayer interference of the fabricated periodic photonic architecture inspired by Papilio palinurus butterfly wings to enhance the spectral diversity of reflectance. Therefore, a one-of-a-kind sensing platform integrates the advantages of MIP and bioinspired photonic structure is demonstrated to actualize distinctive signal conversion and amplification for qualitative and quantitative detection of trace c-Myc protein, accompanied with superior sensitivity (detection limit is 0.014 µg mL-1 ), selectivity, stability, anti-interference ability as well as rapid response/recovery time. This sensor microchip uniquely ventures into the territory of functionally combining bioinspired photonic structure with MIP absorbers, proven promising for prevention or diagnosis of cancers in medical field.
Differential and substrate-specific inhibition of γ-secretase by the C-terminal region of ApoE2, ApoE3, and ApoE4
Authors: Xianglong Hou, Xuexin Zhang, Huan Zou, Mingfeng Guan, Chaoying Fu, Wenyuan Wang, Zai-Rong Zhang, Yang Geng, Yelin Chen
Journal: Neuron (2023)
Prior anti-CTLA-4 therapy impacts molecular characteristics associated with anti-PD-1 response in advanced melanoma
Authors: Katie M. Campbell, Meelad Amouzgar, Shannon M. Pfeiffer, Timothy R. Howes, Egmidio Medina, Michael Travers, Gabriela Steiner, Jeffrey S. Weber, Jedd D. Wolchok, James Larkin, F. Stephen Hodi, Silvia Boffo, Lisa Salvador, Daniel Tenney, Tracy Tang, Marshall A. Thompson, Christine N. Spencer, Daniel K. Wells, Antoni Ribas
Journal: Cancer Cell (2023)

Immune checkpoint inhibitors (ICIs), including CTLA-4- and PD-1-blocking antibodies, can have profound effects on tumor immune cell infiltration that have not been consistent in biopsy series reported to date. Here, we analyze seven molecular datasets of samples from patients with advanced melanoma (N = 514) treated with ICI agents to investigate clinical, genomic, and transcriptomic features of anti-PD-1 response in cutaneous melanoma. We find that prior anti-CTLA-4 therapy is associated with differences in genomic, individual gene, and gene signatures in anti-PD-1 responders. Anti-CTLA-4-experienced melanoma tumors that respond to PD-1 blockade exhibit increased tumor mutational burden, inflammatory signatures, and altered cell cycle processes compared with anti-CTLA-4-naive tumors or anti-CTLA-4-experienced, anti-PD-1-nonresponsive melanoma tumors. We report a harmonized, aggregate resource and suggest that prior CTLA-4 blockade therapy is associated with marked differences in the tumor microenvironment that impact the predictive features of PD-1 blockade therapy response.
Time to Benefit With Sotagliflozin in Patients With Worsening Heart Failure
Authors: Subodh Verma, Deepak L. Bhatt, Nitish K. Dhingra, Ph. Gabriel Steg, Michael Szarek, Michael Davies, Marco Metra, Lars H. Lund, Bertram Pitt
Journal: Journal of the American College of Cardiology (2023)
Effect of the 23-valent pneumococcal polysaccharide vaccine on the incidence of hospitalization with pneumonia in adults aged ≥65 years: retrospective cohort study using a population-based database in Japan
Authors: Hayato Yamana, Sachiko Ono, Nobuaki Michihata, Kohei Uemura, Taisuke Jo, Hideo Yasunaga
Journal: Clinical Microbiology and Infection (2023)
Maximum likelihood pandemic-scale phylogenetics
Authors: Nicola De Maio, Prabhav Kalaghatgi, Yatish Turakhia, Russell Corbett-Detig, Bui Quang Minh, Nick Goldman
Journal: Nature Genetics (2023)

Abstract Phylogenetics has a crucial role in genomic epidemiology. Enabled by unparalleled volumes of genome sequence data generated to study and help contain the COVID-19 pandemic, phylogenetic analyses of SARS-CoV-2 genomes have shed light on the virus’s origins, spread, and the emergence and reproductive success of new variants. However, most phylogenetic approaches, including maximum likelihood and Bayesian methods, cannot scale to the size of the datasets from the current pandemic. We present ‘MAximum Parsimonious Likelihood Estimation’ (MAPLE), an approach for likelihood-based phylogenetic analysis of epidemiological genomic datasets at unprecedented scales. MAPLE infers SARS-CoV-2 phylogenies more accurately than existing maximum likelihood approaches while running up to thousands of times faster, and requiring at least 100 times less memory on large datasets. This extends the reach of genomic epidemiology, allowing the continued use of accurate phylogenetic, phylogeographic and phylodynamic analyses on datasets of millions of genomes.
Advanced glycation end-products as mediators of the aberrant crosslinking of extracellular matrix in scarred liver tissue
Authors: Cheng Lyu, Wenyu Kong, Zhiqiang Liu, Sihan Wang, Peng Zhao, Kaini Liang, Yudi Niu, Wei Yang, Canhong Xiang, Xiaoyu Hu, Xueming Li, Yanan Du
Journal: Nature Biomedical Engineering (2023)
Landscape of prostate-specific membrane antigen heterogeneity and regulation in AR-positive and AR-negative metastatic prostate cancer
Authors: Martin K. Bakht, Yasutaka Yamada, Sheng-Yu Ku, Varadha Balaji Venkadakrishnan, Joshua A. Korsen, Teja M. Kalidindi, Kei Mizuno, Shin Hye Ahn, Ji-Heui Seo, Maria Mica Garcia, Francesca Khani, Olivier Elemento, Henry W. Long, Alain Chaglassian, Nagavarakishore Pillarsetty, Jason S. Lewis, Matthew Freedman, Anthony P. Belanger, Quang-De Nguyen, Himisha Beltran
Journal: Nature Cancer (2023)
Restraint of IFN-γ expression through a distal silencer CNS–28 for tissue homeostasis
Authors: Kairong Cui, Zuojia Chen, Yaqiang Cao, Shuai Liu, Gang Ren, Gangqing Hu, Difeng Fang, Danping Wei, Chengyu Liu, Jinfang Zhu, Chuan Wu, Keji Zhao
Journal: Immunity (2023)
A proteo-transcriptomic map of non-alcoholic fatty liver disease signatures
Authors: Olivier Govaere, Megan Hasoon, Leigh Alexander, Simon Cockell, Dina Tiniakos, Mattias Ekstedt, Jörn M. Schattenberg, Jerome Boursier, Elisabetta Bugianesi, Vlad Ratziu, Ann K. Daly, Quentin M. Anstee
Journal: Nature Metabolism (2023)

Abstract Non-alcoholic fatty liver disease (NAFLD) is a common, progressive liver disease strongly associated with the metabolic syndrome. It is unclear how progression of NAFLD towards cirrhosis translates into systematic changes in circulating proteins. Here, we provide a detailed proteo-transcriptomic map of steatohepatitis and fibrosis during progressive NAFLD. In this multicentre proteomic study, we characterize 4,730 circulating proteins in 306 patients with histologically characterized NAFLD and integrate this with transcriptomic analysis in paired liver tissue. We identify circulating proteomic signatures for active steatohepatitis and advanced fibrosis, and correlate these with hepatic transcriptomics to develop a proteo-transcriptomic signature of 31 markers. Deconvolution of this signature by single-cell RNA sequencing reveals the hepatic cell types likely to contribute to proteomic changes with disease progression. As an exemplar of use as a non-invasive diagnostic, logistic regression establishes a composite model comprising four proteins (ADAMTSL2, AKR1B10, CFHR4 and TREM2), body mass index and type 2 diabetes mellitus status, to identify at-risk steatohepatitis.
Community-integrated self-collected HPV-based cervix screening in a low-resource rural setting: a pragmatic, cluster-randomized trial
Authors: Anna Gottschlich, Beth A. Payne, Jessica Trawin, Arianne Albert, Jose Jeronimo, Sheona Mitchell-Foster, Nadia Mithani, Ruth Namugosa, Priscilla Naguti, Heather Pedersen, Angeli Rawat, Princess Nothemba Simelela, Joel Singer, Laurie W. Smith, Dirk van Niekerk, Jackson Orem, Carolyn Nakisige, Gina Ogilvie
Journal: Nature Medicine (2023)
Reference values for six-minute walk distance and six-minute walk work in Caucasian adults
Authors: J.M. Delbressine, D. Jensen, A.W. Vaes, P.Z. Li, J. Bourbeau, W.C. Tan, B. Hajian, A.J. van ’t Hul, M.A. Spruit
Journal: Pulmonology (2023)

The six-minute walk test (6MWT) is a practical and simple field-based test to assess physical capacity. Several reference equations for six-minute walking distance (6MWD, m) exist, but have a number of limitations that decrease their clinical utility. In addition, no reference equations exist for the 6MWT-derived outcome six-minute walk work (6MWORK, kg.m).To establish new reference equations for 6MWD and 6MWORK on a 20 m course using data from the population-based Canadian Cohort Obstructive Lung Disease study.A total of 335 participants without obstructive or restrictive pulmonary function, with normal self-reported health status, normal exercise capacity, and <30 pack years cigarette smoking history were selected to create a representative sample of Canadian adults aged ≥40 years. All participants performed two 6MWTs. Reference equations were derived using multiple regression analyses.On average, 6MWD and 6MWORK were 541±98 m and 41.3 ± 11.2 kg.m, respectively. All outcomes were significantly greater in males than females. Sex-specific reference equations were derived from the results of 6MWD and 6MWORK with an explained variance of 24 to 35%.This study established reference equations for 6MWD and 6MWORK on a 20 m course in Caucasian males and females aged ≥40 years with normal pulmonary function, self-reported health status and exercise capacity. These newly derived reference equations add value to the assessment of functional capacity in clinical practice.
Achieving Equity in Hospital Performance Assessments Using Composite Race-Specific Measures of Risk-Standardized Readmission and Mortality Rates for Heart Failure
Authors: Amgad Mentias, Eric D. Peterson, Neil Keshvani, Dharam J. Kumbhani, Clyde W. Yancy, Alanna A. Morris, Larry A. Allen, Saket Girotra, Gregg C. Fonarow, Randall C. Starling, Paulino Alvarez, Milind Y. Desai, Peter Cram, Ambarish Pandey
Journal: Circulation (2023)

The contemporary measures of hospital performance for heart failure hospitalization and 30-day risk-standardized readmission rate (RSRR) and risk-standardized mortality rate (RSMR) are estimated using the same risk adjustment model and overall event rate for all patients. Thus, these measures are mainly driven by the care quality and outcomes for the majority racial and ethnic group, and may not adequately represent the hospital performance for patients of Black and other races.
DT-109 ameliorates nonalcoholic steatohepatitis in nonhuman primates
Authors: Pengxiang Qu, Oren Rom, Ke Li, Linying Jia, Xiaojing Gao, Zhipeng Liu, Shusi Ding, Mingming Zhao, Huiqing Wang, Shuangshuang Chen, Xuelian Xiong, Ying Zhao, Chao Xue, Yang Zhao, Chengshuang Chu, Bo Wen, Alexandra C. Finney, Zuowen Zheng, Wenbin Cao, Jinpeng Zhao, Liang Bai, Sihai Zhao, Duxin Sun, Rong Zeng, Jiandie Lin, Wanqing Liu, Lemin Zheng, Jifeng Zhang, Enqi Liu, Y. Eugene Chen
Journal: Cell Metabolism (2023)

Nonalcoholic steatohepatitis (NASH) prevalence is rising with no pharmacotherapy approved. A major hurdle in NASH drug development is the poor translatability of preclinical studies to safe/effective clinical outcomes, and recent failures highlight a need to identify new targetable pathways. Dysregulated glycine metabolism has emerged as a causative factor and therapeutic target in NASH. Here, we report that the tripeptide DT-109 (Gly-Gly-Leu) dose-dependently attenuates steatohepatitis and fibrosis in mice. To enhance the probability of successful translation, we developed a nonhuman primate model that histologically and transcriptionally mimics human NASH. Applying a multiomics approach combining transcriptomics, proteomics, metabolomics, and metagenomics, we found that DT-109 reverses hepatic steatosis and prevents fibrosis progression in nonhuman primates, not only by stimulating fatty acid degradation and glutathione formation, as found in mice, but also by modulating microbial bile acid metabolism. Our studies describe a highly translatable NASH model and highlight the need for clinical evaluation of DT-109.
High Polygenic Risk Is Associated with Earlier Initiation and Escalation of Treatment in Early Primary Open-Angle Glaucoma
Authors: Henry N. Marshall, Sean Mullany, Xikun Han, Ayub Qassim, Weixiong He, Mark M. Hassall, Joshua Schmidt, Daniel Thomson, Thi Thi Nguyen, Ella C. Berry, Lachlan S.W. Knight, Georgina L. Hollitt, Bronwyn Ridge, Angela Schulz, Richard A. Mills, Paul R. Healey, Ashish Agar, Anna Galanopoulos, John Landers, Stuart L. Graham, Alex W. Hewitt, Robert J. Casson, Stuart MacGregor, Owen M. Siggs, Jamie E. Craig
Journal: Ophthalmology (2023)
Cardiovascular Health and Life Expectancy Among Adults in the United States
Authors: Hao Ma, Xuan Wang, Qiaochu Xue, Xiang Li, Zhaoxia Liang, Yoriko Heianza, Oscar H. Franco, Lu Qi
Journal: Circulation (2023)

Cardiovascular disease may be the main reason for stagnant growth in life expectancy in the United States since 2010. The American Heart Association recently released an updated algorithm for evaluating cardiovascular health (CVH)-Life's Essential 8 (LE8) score. We aimed to quantify the associations of CVH levels, estimated by the LE8 score, with life expectancy in a nationally representative sample of US adults.
Evolving Science on Cardiovascular Disease Among Hispanic/Latino Adults
Authors: Amber Pirzada, Jianwen Cai, Gerardo Heiss, Daniela Sotres-Alvarez, Linda C. Gallo, Marston E. Youngblood, M. Larissa Avilés-Santa, Hector M. González, Carmen R. Isasi, Robert Kaplan, John Kunz, James P. Lash, David J. Lee, Maria M. Llabre, Frank J. Penedo, Carlos J. Rodriguez, Neil Schneiderman, Tamar Sofer, Gregory A. Talavera, Bharat Thyagarajan, Sylvia Wassertheil-Smoller, Martha L. Daviglus
Journal: Journal of the American College of Cardiology (2023)
Prognostic impact of increased lymph node yield in colorectal cancer patients with synchronous liver metastasis: a population-based retrospective study of the US database and a Chinese registry
Authors: Shuai Jiao, Xu Guan, Ran Wei, Weiyuan Zhang, Guiyu Wang, Xishan Wang
Journal: International Journal of Surgery (2023)

The National Quality Forum has endorsed at least 12 lymph node yield (LNY) as a surgical quality indicator in colorectal cancer (CRC), but the prognostic value of adequate lymphadenectomy has rarely been investigated for CRC patients with distant metastatic disease.A total of 4575 CRC patients with synchronous liver metastasis who underwent primary tumor resection were identified from a Chinese registry and the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017. The Kaplan-Meier methods and Cox regression models were performed to assess the correlations between LNY and 3-year cancer-specific survival (CSS). Propensity score matching were used to confirmed the survival comparison between patients with less than 12 and of at least 12 LNY.The retrieval of at least 12 LNY was identified in most CRC patients (SEER database, 3380/3899, 86.7%; Chinese cohort, 565/676, 83.6%). In both the SEER database and the Chinese cohort, the patients with LNY ≥12 was significantly associated with better CSS compared with patients with LNY <12 before and after propensity score matching, with all P -value less than 0.05. After controlling for the confounders, multivariate analysis demonstrated that LNY was also an independent prognostic factor for patients with distant metastasis in both cohorts. In subgroup analysis, the CSS benefit for patients with LNY ≥12 was observed across most of the subgroups.Clinical feasibility of the 12-node threshold as a guideline quality metric of cancer care for CRC patients is necessary, and an oncologically adequate lymphadenectomy is still a critical component of high-quality surgical standard in CRC patients with distant metastases.
Commentary on: ‘Postoperative morbidity and weight loss after revisional bariatric surgery for primary failed restrictive procedure: a systematic review and network meta-analysis’
Authors: Rui Yang, Xiaotao Wang, Heyue Wang, Jianli Han
Journal: International Journal of Surgery (2023)

aDepartment of General Surgery, Shanxi Bethune Hospital, Shanxi, China, 030032 bDepartment of General Surgery, Third Hospital of Shanxi Medical University, Shanxi, China, 030032 Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: China. E-mail address: [email protected] (J. Han). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/